Primary biliary cirrhosis: a multi‐faced interactive disease involving genetics, environment and the immune responseUibo, Raivo; Kisand, Kai; Yang, Chen‐Yen; Gershwin, M. Eric
doi: 10.1111/j.1600-0463.2012.02914.xpmid: 23009110
Primary biliary cirrhosis (PBC) is considered a model autoimmune disease based on several features, including the presence of a highly directed and very specific immune response to mitochondrial autoantigens, a female predominance, a targeted destruction of the biliary epithelium, and homogeneity between patients. It is essentially a chronic progressive cholestatic liver disease characterized by immune‐mediated destruction of small‐ and medium‐sized intrahepatic bile ducts. There is considerable variation in the incidence and prevalence of the disease between regions of the world, although such differences likely reflect not only a true disparity in disease but also differences in awareness; for example, in the United States, PBC is often detected in an asymptomatic stage based on multi‐phasic clinical testing. There has been considerable progress at defining the immune response in this disease, including quantitation of autoreactive T cells against PDC‐E2, the major mitochondrial autoantigen. The overwhelming data suggests that patients develop PBC based on a genetic predisposition and loss of tolerance to one or more environmental agents. In this review, we will present an updated overview of PBC and place it in the context of autoimmunity.
Expression of T oll‐like receptor9 in diffuse large B ‐cell lymphoma: further exploring CpG oligodeoxynucleotide in NFκB pathwayHuang, Wan‐Ting; Weng, Shao‐Wen; Huang, Chao‐Cheng; Lin, Huei‐Chiou; Tsai, Po‐Chin; Chuang, Jiin‐Haur
doi: 10.1111/j.1600-0463.2012.02915.xpmid: 23009111
Human Toll‐like receptors (TLRs) that recognize a variety of pathogen‐associated molecular patterns are associated with activation and immunogenic response in lymphoid neoplasms, but rarely explored in diffuse large B‐cell lymphoma (DLBCL). We conducted this study to evaluate the expression of TLR9 in and potential treatment of DLBCL with TLR9 agonist – CpG oligodeoxynucleotide (ODN). The real‐time quantitative reverse transcription‐polymerase chain reaction was carried out to detect TLR9 expression in 41 formalin‐fixed paraffin‐embedded samples. The transformation of immunophenotype and NFκB pathway of DLBCL upon CpG ODN stimulation were investigated by a DLBCL cell line. TLR9 was commonly detected in DLBCL with relative mRNA levels above 1.0 × 10−2 in 35 of 41 cases (85.36%). It was suspected that a high proportion of DLBCL to be activated by CpG stimulation. In vitro study with a DLBCL cell line revealed an increased CD20, but decreased BCL‐6 and MUM1/IRF4 expression after treatment with CpG ODN. The NFκB pathway was initially activated, but finally suppressed upon CpG ODN stimulation. The proliferation of tumor cells was also inhibited by long time incubation. These findings provide new insights into the role of TLR9 in DLBCL and potential implication of TLR9 agonist in the treatment of DLBCL.
TP53 mutations in astrocytic gliomas: an association with histological grade, TP53 codon 72 polymorphism and p53 expressionFaria, Mario H. G.; Neves Filho, Eduardo H. C.; Alves, Markenia K. S.; Burbano, Rommel M. R.; Moraes Filho, Manoel O.; Rabenhorst, Silvia H. B.
doi: 10.1111/j.1600-0463.2012.02918.xpmid: 23009112
TP53 mutations and polymorphisms have been widely related to many cancers as long as these alterations may impair its capacity to induce cell cycle arrest, DNA repair mechanisms, and apoptosis. Although TP53 alterations have been studied in astrocytic tumors, there is a lack of analysis considering specific TP53 mutations and their associations with p53 immunostainning, polymorphisms and their significance among the histological grades. Thus, we analyzed TP53 alterations in exons 2–11, including the codon 72 polymorphism, using DNA sequencing in 96 astrocytic gliomas (18 grade I, 20 grade II, 14 grade III, and 44 grade IV). Also, immunohistochemistry was assessed to evaluate the p53 protein expression. In this study, we found that the higher histological grades were statistically associated with TP53 mutations. Some of these mutations, such as TP53 P98T and TP53 G244S, seemed to be a specific marker for the higher grades, and the TP53 E286K mutation appears to be a World Health Organization grade III–IV progression marker. Also, the TP53 P98T mutation, in exon 4, is very likely to be important on the stabilization of the p53 protein, leading to its immunopositivity and it is potentially associated with the TP53 72Pro/Pro genotype.
Altered expression of p27 Kip1 ‐interacting cell‐cycle regulators in the adult testicular germ cell tumors: potential role in tumor development and histological progressionMiyai, Kosuke; Yamamoto, Sohei; Iwaya, Keiichi; Asano, Tomohiko; Tamai, Seiichi; Tsuda, Hitoshi; Matsubara, Osamu
doi: 10.1111/j.1600-0463.2012.02919.xpmid: 23009113
We examined the potential role of cell‐cycle dysregulation in the development and histological progression of adult testicular germ cell tumors (TGCTs). Expressions of p27Kip1‐interacting cell‐cycle regulators (down‐regulation of p27Kip1 and overexpression of Skp2, Cks1, cyclin A, and cyclin E) and Ki‐67 labeling index (LI) were immunohistochemically examined in histological components of 50 intratubular germ cell neoplasms, unclassified (IGCNUs); 74 seminomas; and 25 embryonal carcinomas, identified from 88 patients. Altered expression of p27Kip1, Skp2, Cks1, cyclin A, and cyclin E was observed in 20%, 12%, 16%, 10%, and 24% of IGCNUs; 26%, 36%, 27%, 89%, and 23% of seminomas; and 48%, 68%, 56%, 100%, and 60% of embryonal carcinomas, respectively. A significant difference in the frequency of Skp2 and cyclin A overexpression was observed between IGCNUs and seminomas. Significantly more frequent alterations of Skp2, Cks1, and cyclin E and p27Kip1 were detected in embryonal carcinomas than in seminomas. Alterations of all cell‐cycle regulators were significantly more frequent in embryonal carcinomas than in IGCNUs. The mean Ki‐67 LI significantly increased from IGCNU (21.2%) through seminoma (34.7%) to embryonal carcinoma (54.2%). These results suggest that alterations of the p27Kip1‐interacting cell‐cycle regulators are common in TGCTs and may be involved in their histological progression.
Antibiotic resistance and molecular epidemiology of the beta‐lactamase‐producing H aemophilus influenzae isolated in Chongqing, ChinaLuo, Chong; Xia, Yongwu; Liu, Qian; Chu, Lijuan; Fu, Xiaohong; Jing, Chunmei; Chen, Dapeng; Liu, Lan; Shi, Yu
doi: 10.1111/j.1600-0463.2012.02921.xpmid: 23009117
This study aimed to determine the antibiotic resistance and molecular epidemiology of Haemophilus influenzae isolated from children with acute respiratory infection in Chongqing, China. To this end, 1967 H. influenzae isolates from 2006 to 2009 were analysed regarding β‐lactamase production and antibiotic resistance. Ninety‐nine β‐lactamase‐producing H. influenzae isolates from 2010 were analysed for antibiotic resistance and promoter regions of blaTEM‐1. β‐lactamase production was found in 35.8% (705/1967) of the strains. All ninety‐nine β‐lactamase‐producing strains from 2010 were of the TEM‐1 type as determined by PCR but did not produce the predicted 1075 bp product. According to PCR‐SSCP and DNA sequencing, the promoter regions of blaTEM‐1 were categorized into 6 genotypes as SSCP1 (Pdel), SSCP2 (Pa/Pb), SSCP3 (P4), SSCP4 (Prpt.b), SSCP5 (2Prpt) and SSCP6 (P3.b). The Pdel, Pa/Pb and Prpt.b were common promoters of blaTEM‐1 for H. influenzae isolated from children in Chongqing. Strains with Prpt.b were more resistant to ampicillin (AMP) than strains with Pdel, Pa/Pb and P4 (p < 0.05). Therefore, blaTEM‐1 β‐lactamase is the main mechanism for resistance of H. influenzae to ampicillin in Chongqing. Furthermore, the Prpt.b promoters may be related to the high resistance of H. influenzae to AMP.